Distinct Features of Vascular Diseases in COVID-19

Abstract

The Coronavirus Disease 2019 (COVID-19) pandemic was declared in early 2020 after several unexplained pneumonia cases were first reported in Wuhan, China, and subsequently in other parts of the world. Commonly, the disease comprises several clinical features, including high temperature, dry cough, shortness of breath, and hypoxia, associated with findings of interstitial pneumonia on chest X-ray and computer tomography. Nevertheless, severe forms of acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are not limited to the respiratory tract but also may be extended to other systems, including the cardiovascular system. The bi-directional relationship between atherosclerosis and COVID-19 is accompanied by poor prognosis. The immune response hyperactivation due to SARS-CoV-2 infection causes an increased secretion of cytokines, endothelial dysfunction, and arterial stiffness, which promotes the development of atherosclerosis. Also, due to the COVID-19 pandemic, access to healthcare amenities was reduced, resulting in increased morbidity and mortality in patients at risk. Furthermore, as lockdown measures were largely adopted worldwide, the sedentary lifestyle and the increased consumption of processed nutrients or unhealthy food increased, and in the consequence, we might observe even 70% of overweight and obese population. Altogether, with the relatively low ratio of vaccinated people in many countries, and important health debt appeared, which is now and will be for next decade a large healthcare challenge. However, the experience gained in the COVID-19 pandemic and the new methods of patients' approaching have helped the medical system to overcome this crisis and will hopefully help in the case of new possible epidemics.

Keywords: COVID-19; SARS-CoV-2; arterial stiffness; atherosclerosis; endothelial dysfunction; vaccines; vascular diseases.

Figure 1

Endothelial dysfunction and vascular inflammation caused by SARS-CoV-2 infection. Circulating SARS-CoV-2 virus induces a systemic inflammatory response, but it can also be taken up by endothelial cells (ECs), likely via binding to the ACE2 receptor. Inside the cell, the viral RNA is recognized by pattern recognition receptors, such as Toll like receptors (TLRs) and generates an inflammatory response through upregulation of NF-κB. In addition, the binding of virus to the ACE2 receptor results in a shift towards increased angiotensin II (AngII)-angiotensin II type 1 (AT1) receptor signalling, which further enhances the production of inflammatory cytokines via the NF-κB pathway. This will lead to increased levels of reactive oxygen species (ROS) and a lower nitric oxide (NO) bioavailability, consequently enabling endothelial dysfunction and stimulating apoptotic cell death. Furthermore, glycocalyx degrading enzymes will give rise to shedding of glycocalyx fragments, tight junctions will be disrupted and together with the increased expression of adhesion molecules, leukocyte recruitment and extravasation are promoted. The upregulation of P-selectin, fibrinogen, von Willebrand factor (vWF) and tissue factor will contribute to platelet aggregation and coagulation, potentially giving rise to thrombotic complications. (Created with BioRender.com).

Figure 2

Overview of COVID-19 related vascular complications. SARS-CoV-2 infection gives rise to enhanced oxidative stress, inflammation and angiotensin II (AngII)-angiotensin II type 1 (AT1) receptor signalling, which ultimately leads to endothelial cell (EC) dysfunction and apoptotic cell death (1). An important consequence of EC dysfunction is the development of arterial stiffness due to impaired nitric oxide bioavailability. Also remodelling of the extracellular matrix, leading to a lower elastin/collagen ratio, contributes to arterial stiffness development (2). The increase in vascular stiffness can further damage ECs, thereby resulting in a vicious cycle. Eventually these pathophysiological mechanisms can drive the development of atherosclerosis, peripheral and coronary artery disease (3). (Created with BioRender.com).